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VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions
Membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and mitochondria are emerging as critical hubs for diverse cellular events, and alterations in the extent of these contacts are linked to neurodegenerative diseases. However, the mechanisms that control ER–mitochondria interactions...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351740/ https://www.ncbi.nlm.nih.gov/pubmed/34133214 http://dx.doi.org/10.1091/mbc.E21-03-0097 |
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author | Du, Yuanjiao Wang, Jingru Xiong, Juan Fang, Na Ji, Wei-Ke |
author_facet | Du, Yuanjiao Wang, Jingru Xiong, Juan Fang, Na Ji, Wei-Ke |
author_sort | Du, Yuanjiao |
collection | PubMed |
description | Membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and mitochondria are emerging as critical hubs for diverse cellular events, and alterations in the extent of these contacts are linked to neurodegenerative diseases. However, the mechanisms that control ER–mitochondria interactions are so far elusive. Here, we demonstrate a key role of vacuolar protein sorting–associated protein 13D (VPS13D) in the negative regulation of ER–mitochondria MCSs. VPS13D suppression results in extensive ER–mitochondria tethering, a phenotype that can be substantially rescued by suppression of the tethering proteins VAPB and PTPIP51. VPS13D interacts with valosin-containing protein (VCP/p97) to control the level of ER-resident VAPB at contacts. VPS13D is required for the stability of p97. Functionally, VPS13D suppression leads to severe defects in mitochondrial morphology, mitochondrial cellular distribution, and mitochondrial DNA synthesis. Together, our results suggest that VPS13D negatively regulates the ER–mitochondria MCSs, partially through its interactions with VCP/p97. |
format | Online Article Text |
id | pubmed-8351740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-83517402021-10-16 VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions Du, Yuanjiao Wang, Jingru Xiong, Juan Fang, Na Ji, Wei-Ke Mol Biol Cell Articles Membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and mitochondria are emerging as critical hubs for diverse cellular events, and alterations in the extent of these contacts are linked to neurodegenerative diseases. However, the mechanisms that control ER–mitochondria interactions are so far elusive. Here, we demonstrate a key role of vacuolar protein sorting–associated protein 13D (VPS13D) in the negative regulation of ER–mitochondria MCSs. VPS13D suppression results in extensive ER–mitochondria tethering, a phenotype that can be substantially rescued by suppression of the tethering proteins VAPB and PTPIP51. VPS13D interacts with valosin-containing protein (VCP/p97) to control the level of ER-resident VAPB at contacts. VPS13D is required for the stability of p97. Functionally, VPS13D suppression leads to severe defects in mitochondrial morphology, mitochondrial cellular distribution, and mitochondrial DNA synthesis. Together, our results suggest that VPS13D negatively regulates the ER–mitochondria MCSs, partially through its interactions with VCP/p97. The American Society for Cell Biology 2021-08-01 /pmc/articles/PMC8351740/ /pubmed/34133214 http://dx.doi.org/10.1091/mbc.E21-03-0097 Text en © 2021 Du et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/3.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Du, Yuanjiao Wang, Jingru Xiong, Juan Fang, Na Ji, Wei-Ke VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions |
title | VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions |
title_full | VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions |
title_fullStr | VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions |
title_full_unstemmed | VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions |
title_short | VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions |
title_sort | vps13d interacts with vcp/p97 and negatively regulates endoplasmic reticulum–mitochondria interactions |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351740/ https://www.ncbi.nlm.nih.gov/pubmed/34133214 http://dx.doi.org/10.1091/mbc.E21-03-0097 |
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